An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19 | Zendy

Dafydd R. Owen | Zendy; Charlotte Allerton | Zendy; Annaliesa S. Anderson | Zendy; Lisa Aschenbrenner | Zendy; Melissa Avery | Zendy; Simon Berritt | Zendy; Britton Boras | Zendy; Rhonda D. Cardin | Zendy; Anthony Carlo | Zendy; Karen J. Coffman | Zendy; Alyssa Dantonio | Zendy; Li Di | Zendy; Heather Eng | Zendy; Rose Ann Ferre | Zendy; K.S. Gajiwala | Zendy; Scott Gibson | Zendy; S.E. Greasley | Zendy; Brett L. Hurst | Zendy; Eugene P. Kadar | Zendy; Amit S. Kalgutkar | Zendy; Jack C. Lee | Zendy; Jisun Lee | Zendy; Wei Liu | Zendy; Stephen W. Mason | Zendy; Stephen Noell | Zendy; Jonathan J. Novak | Zendy; R. Scott Obach | Zendy; Kevin Ogilvie | Zendy; Nandini C. Patel | Zendy; Martin Pettersson | Zendy; K. Devendra | Zendy; Matthew R. Reese | Zendy; M. F. Sammons | Zendy; Jean G. Sathish | Zendy; Ravi Shankar Prasad Singh | Zendy; Claire M. Steppan | Zendy; Al Stewart | Zendy; Jamison B. Tuttle | Zendy; Lawrence W. Updyke | Zendy; Patrick R. Verhoest | Zendy; Liuqing Wei | Zendy; Qingyi Yang | Zendy; Yuao Zhu | Zendy

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An oral SARS-CoV-2 M ^pro inhibitor clinical candidate for the treatment of COVID-19

Author(s) -

Dafydd R. Owen,

Charlotte Allerton,

Annaliesa S. Anderson,

Lisa Aschenbrenner,

Melissa Avery,

Simon Berritt,

Britton Boras,

Rhonda D. Cardin,

Anthony Carlo,

Karen J. Coffman,

Alyssa Dantonio,

Li Di,

Heather Eng,

Rose Ann Ferre,

K.S. Gajiwala,

Scott Gibson,

S.E. Greasley,

Brett L. Hurst,

Eugene P. Kadar,

Amit S. Kalgutkar,

Jack C. Lee,

Jisun Lee,

Wei Liu,

Stephen W. Mason,

Stephen Noell,

Jonathan J. Novak,

R. Scott Obach,

Kevin Ogilvie,

Nandini C. Patel,

Martin Pettersson,

K. Devendra,

Matthew R. Reese,

M. F. Sammons,

Jean G. Sathish,

Ravi Shankar Prasad Singh,

Claire M. Steppan,

Al Stewart,

Jamison B. Tuttle,

Lawrence W. Updyke,

Patrick R. Verhoest,

Liuqing Wei,

Qingyi Yang,

Yuao Zhu

Publication year - 2021

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.abl4784

Subject(s) - potency , outbreak , covid-19 , in vivo , virology , pandemic , coronavirus , clinical trial , pharmacology , in vitro , protease inhibitor (pharmacology) , medicine , chemistry , biology , virus , viral load , disease , biochemistry , infectious disease (medical specialty) , microbiology and biotechnology , antiretroviral therapy

Path to another drug against COVID-19 The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owenet al . report the discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication. The drug, PF-07321332, can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model. In a phase 1 clinical trial, the drug reached concentrations expected to inhibit the virus based on in vitro studies. It also inhibited other coronaviruses, including severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, and could be in the armory against future viral threats. —VV

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